Lead poisoning remains a major health problem in the United States. Up to 19% of the children from a recent series of screening programs from 1969-1971 had lead blood levels of 60 micrograms/100 ml or higher, concentrations that are generally accepted as severe enough to require medical treatment. Lead is known to be toxic to the erythropoietic system, producing anemia. A possible explanation for this anemia is inhibition of heme biosynthesis in erythropoietic tissue. The goal of the research proposed in this project is to elucidate the role of a dialyzable, protective factor against lead inhibition of uroporphyrinogen I synthetase, an enzyme midway along the heme synthetic pathway. Results of preliminary experiments have demonstrated that this factor is present in the liver and offers complete protection against lead inhibition of hepatic uroporphyrinogen I synthetase activity. However, this factor is evidently not present in the erythrocyte, or is present at a lower concentration, since lead is a potent inhibitor of hemolysate enzyme. The results of studies directed towards understanding this protection against lead inhibition of this enzymatic step of heme biosynthesis by this dialyzable factor will provide valuable information on mechanisms of lead toxicity and new information on the possible treatment of lead intoxication. BIBLIOGRAPHIC REFERENCE: E. Kun, E. Kirsten and W. N. Piper, Stabilization of mitochondrial functions with digitonin, in press, Methods Enzymol., Academic Press, New York (1977). W.N. Piper, G. Rios and T.R. Tephly, Studies on the role of a factor protecting against lead inhibition of erythrocytic and hepatic uroporphyrinogen I synthetase activity, In: Biological implications of metals in the environment, ed. H. Drucker, in press, ERDA symposium, National Technical Information Service, Springfield, Virginia (1977).